Clinical Trials Register

Summary
EudraCT Number:	2009-016095-68
Sponsor's Protocol Code Number:	M10-877
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-06-17
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2009-016095-68

A.3

Full title of the trial

A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab as Maintenance Therapy in Subjects Requiring High Dose Corticosteroids for Active Non infectious Intermediate-, Posterior-, or Pan-uveitis

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study comparing the safety and efficacy of Adalimumab vs. Placebo in subjects with active uveitis

A.3.2

Name or abbreviated title of the trial where available

N/A

A.4.1

Sponsor's protocol code number

M10-877

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AbbVie Deutschland GmbH & Co. KG
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AbbVie Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AbbVie Ltd.
B.5.2	Functional name of contact point	Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Abbott House, Vanwall Business Park,
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4XE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 1628 644330
B.5.5	Fax number	+44 1628 644475
B.5.6	E-mail	euclinicaltrials@abbott.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Humira 40 mg solution for injection in pre-filled syringes
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott Laboratories Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Active Non-infectious Intermediate-, Posterior-, or Pan-uveitis

E.1.1.1

Medical condition in easily understood language

Uveitis refers to inflammation in the uveal tract of the eye which includes the iris, ciliary body, and choroid.

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10022557
E.1.2	Term	Intermediate uveitis
E.1.2	System Organ Class	100000004853

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10036370
E.1.2	Term	Posterior uveitis
E.1.2	System Organ Class	100000004862

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10033687
E.1.2	Term	Panuveitis
E.1.2	System Organ Class	100000004853

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objective of this study is to evaluate the efficacy and safety of adalimumab 80 mg loading dose followed by 40 mg dose given every other week (eow) subcutaneously (SC) starting at Week 1 compared with placebo as maintenance therapy in subjects requiring high dose corticosteroids for active non-infectious intermediate-, posterior-, or pan-uveitis.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subject is ≥ 18 years of age.

Subject is diagnosed with non-infectious intermediate-, posterior- or pan-uveitis.

Subject must have active disease at the Baseline visit as defined by the presence of at least 1 of the following parameters in at least one eye despite at least 2 weeks of maintenance therapy with oral prednisone at a dose of ≥ 10 mg/day to ≤ 60 mg/day (or oral corticosteroid equivalent):

● Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion
● ≥ 2+ anterior chamber cells (Standardization of Uveitis Nomenclature [SUN] criteria)
● ≥ 2+ vitreous haze (National Eye Institute [NEI]/SUN criteria)

Subject is on oral prednisone at a dose of ≥ 10 mg/day to ≤ 60 mg/day (or oral corticosteroid equivalent) for at least 2 weeks prior to Screening and remains on the same dose from Screening to Baseline visit.

Subjects who do not have previous, active or latent TB.

E.4

Principal exclusion criteria

1. Subject with isolated anterior uveitis.
2. Subject with prior inadequate response to high-dose oral corticosteroids.
3. Subject with confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus (CMV), Lyme disease, toxoplasmosis, Human T-Lymphotropic Virus Type 1 (HTLV-1) infection, Whipple's disease, herpes zoster virus (HZV) and herpes simplex virus (HSV).
4. Subject with presumed ocular histoplasmosis syndrome (POHS).
5. Subject with ocular masquerade syndromes, such as ocular lymphoma.
6. Subject with serpiginous choroidopathy.
7. Subject has a contraindication to pupil dilation with mydriatic eyedrops.
8. Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial.
9. Subject with intraocular pressure of ≥ 25 mmHg and on ≥ 2 glaucoma medications or evidence of glaucomatous optic nerve injury.
10. Subject with Best Corrected Visual Acuity (BCVA) less than 20 letters (ETDRS [Early Treatment Diabetic Retinopathy Study]) in at least one eye.
11. Subject with intermediate uveitis or panuveitis that has signs of intermediate uveitis (e.g., presence or history of snowbanking or snowballs) and symptoms and/or Magnetic Resonance Imaging (MRI) findings suggestive of a demyelinating disease such as multiple sclerosis. All subjects with intermediate uveitis or
panuveitis that have signs of intermediate uveitis (e.g., presence or history of snowbanking or snowballs) must have a brain MRI within 90 days prior to the Baseline visit.
12. Subject has previous exposure to anti-TNF therapy or any biologic therapy (except intravitreal anti-vascular endothelial growth factor [VEGF] therapy [See Exclusion Criterion No. 43]) with a potential therapeutic impact on non infectious uveitis.
13. Subject on more than 1 immunosuppressive therapy (not including corticosteroids) at Baseline.
14. Subject on concomitant immunosuppressive therapy other than methotrexate, cyclosporine, mycophenolate mofetil or an equivalent drug to mycophenolate mofetil (eg mycophenolic acid), azathioprine or tacrolimus at Baseline.
15. If entering the study on 1 concomitant immunosuppressive therapy, dose has been increased within the last 28 days prior to Baseline visit or is not within the following allowable doses at the Baseline visit:
● Methotrexate (MTX) ≤ 25 mg per week
● Cyclosporine ≤ 4 mg/kg per day
● Mycophenolate mofetil ≤ 2 grams per day or an equivalent drug to mycophenolate mofetil (eg mycophenolic acid) at an equivalent dose approved by the Medical Monitor.
● Azathioprine ≤ 175 mg per day
● Tacrolimus (oral formulation) ≤ 8 mg per day
16. Subject with prior or current use of chlorambucil.
17. Subject has received Retisert® (glucocorticosteroid implant) within 3 years prior to the Baseline visit or has had complications related to the device.
Subject has had Retisert® (glucocorticosteroid implant) removed within 90 days prior to the Baseline visit or has had complications related to the removal of the device.
18. Subject has received intraocular or periocular corticosteroids within 30 days prior to the Baseline visit.
19. Subject with history of prior ocular surgery within 90 days prior to the Baseline visit with the exception of refractive laser surgery or retinal laser photocoagulation or YAG (neodymium-doped yttrium aluminium garnet) posterior capsulotomy. These three exceptions are exclusionary within 30 days prior to Baseline..
20. Subject with any planned (elective) eye surgery within the next 80 weeks from Baseline.
21. Subject with proliferative or severe non-proliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy.
22. Subject with neovascular/wet age-related macular degeneration.
23. Subject with abnormality of vitreo-retinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) with the potential for macular structural damage independent of the inflammatory process.
40. Subject with severe vitreous haze that precludes visualization of the fundus at the Baseline visit.
41. Subject has received Ozurdex® (dexamethasone implant) within 6 months prior to Baseline visit.
42. Subject has received intravitreal MTX within 90 days prior to the Baseline visit.
43. Subject has received intravitreal anti-VEGF therapy:
● within 45 days of the Baseline visit for Lucentis® (ranibizumab) or Avastin® (bevacizumab);
● or within 60 days of the Baseline visit for anti-VEGF Trap (Aflibercept).
51. Subject with intolerance to high-dose oral corticosteroids (equivalent of oral prednisone 1 mg/kg/day or 60 to 80 mg/day).
52. Subject on cyclophosphamide within 30 days prior to the Baseline visit.

E.5 End points

E.5.1

Primary end point(s)

Time to treatment failure. Please refer to section 5.3.3.1 of the study protocol for further information.

E.5.1.1

Timepoint(s) of evaluation of this end point

It will be evaluated at Week 6 and each visit thereafter.

E.5.2

Secondary end point(s)

1. Change in Vitreous Haze grade (NEI/SUN criteria) in each eye from Week 6 to the Final/Early Termination visit.
2. Change in Anterior Chamber (AC) cell grade in each eye from Week 6 to the Final/Early Termination visit.
3. Change in logMAR BCVA in each eye from Week 6 to the Final/Early Termination Visit
4. Time to OCT evidence of macular edema in at least one eye on or after Week 6
5. Change in central retinal thickness in each eye from Week 6 to the Final/Early Termination visit
6. Change in NEI Visual Functioning Questionnaire (VFQ-25) score from Week 6 to the Final/Early Termination visit

E.5.2.1

Timepoint(s) of evaluation of this end point

Please see details in E.5.2.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Austria

Belgium

Brazil

Canada

Czech Republic

Denmark

France

Germany

Greece

Ireland

Israel

Italy

Japan

Mexico

Netherlands

New Zealand

Poland

Portugal

Spain

Switzerland

Turkey

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end-of-study is defined as the date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is later (refer section 13 of the protocol)

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

105

F.4.2.2

In the whole clinical trial

250

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Subjects may be offered the opportunity to enroll into a rollover study (M11-327) if Treatment Failure criteria are met at or after Week 6, the site is participating in the rollover study, and the subject meets all of the inclusion and none of the exclusion criteria for Study M11-327. If the subject does not enter the rollover study, the subject will be treated in accordance wtih the investigator's best clinical judgement.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2010-07-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-09-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-08-21

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